This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the proposed studies I will investigate the hypothesis that the Francisella Pathogenicity Island encodes for proteins that are secreted during infection and influence the infection process as secreted effector proteins. Francisella a facultative intracellular pathogen that is listed as a potential agent of bioterrorism carries a region in its genome that is crucial for intracellular growth and virulence. Some proteins encoded in this region of the Francisella Pathogenicity Island (FPI) have homologies to parts of a Type Six Secretion System (TSSS). I hypothesize that the FPI does not only encode a secretion machinery but also secreted effector proteins of this TSSS. I will test this hypothesis by screening for potentially secreted proteins and describe the temporal and special regulation of these factors in the host cell. In addition I will test if these factors are involved in the described immune regulatory ability of Francisella.